The Role of Mitochondrial Homeostasis and Molecular Regulation of Mitochondrial Biogenesis in the Heart: Current data suggest that mitochondria may play a central role in the promotion of cell survival across multiple cell/tissue types. In the heart (and other organs) a phenomenon named preconditioning seems to activate the cell survival response conferring enhanced tolerance towards ischemic insults. We and others have begun to demonstrate that the mitochondria may be central to the preconditioning phenomenon. This biological phenomenon is being exploited to enhance our understanding of the molecular regulation of mitochondrial function to promote myocardial cell survival in the heart as a putative adaptive modulation in heart failure and in ischemic heart disease. Here we focus on the regulatory control of mitochondrial biogenesis, as a putative adaptive program that could be manipulated to augment cardiac tolerance to ischemia. Furthermore, the role of perturbations in mitochondrial biogenesis in the development and progression of complications of diabetes in the heart is being explored using both cellular models and genetically modified mouse models. Candidate proteins identified that may modulate the mitochondrial biogenesis program in diabetes have been identified and these are being characterized via functional genomics to evaluate their role in the development of mitochondrial dysfunction in diabetes. At the translational level my laboratory explores the modulation of insulin sensitivity in the progression of heart failure in diabetic and pre-diabetic human subjects and we explore various aspects of the preconditioning program.